Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis

Hereditary gingival fibromatosis(HGF)is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity.Five distinct loci related to non-syndromic HGF have been identified;however,only two diseasecausing genes,SOS1 and REST,inducing HGF have been identified at two loci,GINGF1 and GINGF5,respectively.Here,based on a family pedigree with 26 members,including nine patients with HGF,we identified double heterozygous pathogenic mutations in the ZNF513(c.C748T,p.R250W)and KIF3C(c.G1229A,p.R410H)genes within the GINGF3 locus related to HGF.Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo.ZNF513,a transcription factor,binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts.Furthermore,a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513(p.R250W)or Kif3c(p.R412H)alone do not led to clear phenotypes with gingival fibromatosis,whereas the double mutations led to gingival hyperplasia phenotypes.In addition,we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1.Moreover,the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels.ZNF513 combined with KIF3C regulates gingival fibroblast proliferation,migration,and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways.In summary,these results demonstrate ZNF513+KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.

High-Performance Na-Ion Storage of S-Doped Porous Carbon Derived from Conjugated Microporous Polymers

Na-ion batteries(NIBs)have attracted considerable attention in recent years owing to the high abundance and low cost of Na.It is well known that S doping can improve the electrochemical performance of carbon materials for NIBs.However,the current methods for S doping in carbons normally involve toxic precursors or rigorous conditions.In this work,we report a creative and facile strategy for preparing S-doped porous carbons(SCs)via the pyrolysis of conjugated microporous polymers(CMPs).Briefly,thiophene-based CMPs served as the precursors and doping sources simultaneously.Simple direct carbonization of CMPs produced S-doped carbon materials with highly porous structures.When used as an anode for NIBs,the SCs exhibited a high reversible capacity of 440 mAh g?1 at 50 mA g?1 after 100 cycles,superior rate capability,and excellent cycling stability(297 mAh g?1 after 1000 cycles at 500 mA g?1),outperforming most S-doped carbon materials reported thus far.The excellent performance of the SCs is attributed to the expanded lattice distance after S doping.Furthermore,we employed ex situ X-ray photoelectron spectroscopy to investigate the electrochemical reaction mechanism of the SCs during sodiation-desodiation,which can highlight the role of doped S for Na-ion storage.

A hollow tubular NiCo layacknered double hydroxide@Ag nanowire structure for high-power-density flexible aqueous Ni//Zn battery

Flexible aqueous Ni//Zn batteries have attracted much attention as promising candidates for energy storage in the field of flexible electronics.However,the Ni-based cathodes still face the challenges of poor conductivity,confined charge/mass transfer,and non-flexibility.In this work,we designed a hollow tubular structure consisting of a conductive silver nanowire (Ag NW) wrapped by active Ni Co layered double hydroxide (LDH),for enhancing the electrical conductivity,improving the charge/mass transfer kinetics,and facilitating the ion penetration.By optimizing the contents of Ni,Co and Ag NW,the Ni_(4)Co LDH@Ag_(1.5)NW composite shows a maximum specific capacity of 115.83 m Ah g^(-1)at 0.1 A g^(-1)measured in a two-electrode system.Highlightingly,the flexible aqueous Ni//Zn battery assembled by Ni_(4)Co LDH@Ag_(1.5)NW interwoven with multi-walled carbon nanotube cathode and Zn foil anode realizes a high power density of 160μW cm^(-2)at the energy density of 23.14μWh cm^(-2),which is superior compared with those of oxide/hydroxide based devices and even higher than those of many carbon-based supercapacitors,showing its promising potentials for flexible energy storage applications.

Whole exome sequencing identifies an AMBN missense mutation causing severe autosomal-dominant amelogenesis imperfecta and dentin disorders

Tooth development is a complex process that involves precise and time-dependent orchestration of multiple genetic, molecular,and cellular interactions. Ameloblastin(AMBN, also named "amelin" or "sheathlin") is the second most abundant enamel matrix protein known to have a key role in amelogenesis. Amelogenesis imperfecta(AI [MIM: 104500]) refers to a genetically and phenotypically heterogeneous group of conditions characterized by inherited developmental enamel defects. The hereditary dentin disorders comprise a variety of autosomal-dominant genetic symptoms characterized by abnormal dentin structure affecting either the primary or both the primary and secondary teeth. The vital role of Ambn in amelogenesis has been confirmed experimentally using mouse models. Only two cases have been reported of mutations of AMBN associated with non-syndromic human AI. However, no AMBN missense mutations have been reported to be associated with both human AI and dentin disorders.We recruited one kindred with autosomal-dominant amelogenesis imperfecta(ADAI) and dentinogenesis imperfecta/dysplasia characterized by generalized severe enamel and dentin defects. Whole exome sequencing of the proband identified a novel heterozygous C-T point mutation at nucleotide position 1069 of the AMBN gene, causing a Pro to Ser mutation at the conserved amino acid position 357 of the protein. Exfoliated third molar teeth from the affected family members were found to have enamel and dentin of lower mineral density than control teeth, with thinner and easily fractured enamel, short and thick roots, and pulp obliteration. This study demonstrates, for the first time, that an AMBN missense mutation causes non-syndromic human AI and dentin disorders.

On the Range of the Common Cycle Time in a Road Network

In a coordinated road network,the optimal common cycle time is determined by evaluating the performance of the network in the given range of cycles. Normally,this range is determined by users 'experience. And a large range of common cycle time,e. g. [30,200] is chosen,which requires long computation time. This study considers that the optimal common cycle time ranges between the minimal and maximal value of intersections' individual optimal cycle time. It is proved mathematically from the convexity condition,that the delay of the network and each individual intersection are convex functions of the cycle time according to Webster delay model. Finally,2 000 random cases for the network composed of two intersections and of eight intersections are created to underline the proposed conclusions. The results of all cases confirm the validity,and show up to 90% improvement in computation time to compare with experience range. The signal optimization tool,Synchro,is also used to validate the conclusion by 50 random cases. The results confirm reliability further.

Research Advances in Plant Golgi Apparatus

Golgi apparatus,together with endoplasmic reticula,vacuoles and plasma membrane,constitutes the endoplasmic system of plant cells.It plays an important role in the secretion pathway of eukaryotic cells and is responsible for various intracellular events,such as protein classification,protein modification and glycosylation.At present,much less is known about plant Golgi proteins.The research on its function is still insufficient.In order to provide a comprehensive research background and research ideas for related researchers,this paper systematically and comprehensively evaluated the structure of plant endoplasmic system,the common endoplasmic reticulum-Golgi transport pathway in plant cells,various possible transport models between endoplasmic reticula and Golgi bodies,Golgi-associated specific proteins and functions,and Golgi biogenesis pathway.The latest research progress in this field was reviewed and analyzed in detail.This paper will provide an important reference for related researchers to carry out the research of plant Golgi.

Monitoring the green evolution of vernacular buildings based on deep learning and multi-temporal remote sensing images

The increasingly mature computer vision(CV)technology represented by convolutional neural networks(CNN)and available high-resolution remote sensing images(HR-RSIs)provide opportunities to accurately measure the evolution of natural and artificial environments on Earth at a large scale.Based on the advanced CNN method high-resolution net(HRNet)and multi-temporal HR-RSIs,a framework is proposed for monitoring a green evolution of courtyard buildings characterized by their courtyards being roofed(CBR).The proposed framework consists of an expert module focusing on scenes analysis,a CV module for automatic detection,an evaluation module containing thresholds,and an output module for data analysis.Based on this,the changes in the adoption of different CBR technologies(CBRTs),including light-translucent CBRTs(LT-CBRTs)and non-lighttranslucent CBRTs(NLT-CBRTs),in 24 villages in southern Hebei were identified from 2007 to 2021.The evolution of CBRTs was featured as an inverse S-curve,and differences were found in their evolution stage,adoption ratio,and development speed for different villages.LT-CBRTs are the dominant type but are being replaced and surpassed by NLT-CBRTs in some villages,characterizing different preferences for the technology type of villages.The proposed research framework provides a reference for the evolution monitoring of vernacular buildings,and the identified evolution laws enable to trace and predict the adoption of different CBRTs in a particular village.This work lays a foundation for future exploration of the occurrence and development mechanism of the CBR phenomenon and provides an important reference for the optimization and promotion of CBRTs.

Influence of vibration on the grain flow sensor during the harvest and the difference elimination method

The grain yield data collected by the intelligent yield measurement system of the combine harvester is generated into a field plot yield distribution map,which is of great significance for guiding agricultural production.However,in the process of drawing the yield map,the combine harvester is affected by vibration during operation and the generated error data in the process of collecting data which will cause the drawing results to be inaccurate.This study researched two factors that cause errors,then,the influence of vibration interference on the measurement signal was eliminated by filtering,vibration isolation,and designing a double-plates differential grain flow sensor.Three methods were taken to eliminate random errors,gross errors and systematic errors,including using the arithmetic average value to replace the true value,the 3σcriterion,and removing the filling time data and the delaying time data.Finally,the grain yield distribution map was obtained through Matlab and Excel.The results showed that the interference frequency above 50 Hz could be eliminated by filtering,but it was difficult to filter the low-frequency signal which was close to the grain impact frequency.The vibration amplitude was reduced to 14.29%by adding a vibration isolation plate,and the SNR was increased from−4.67 dB to 29.21 dB by combining low-pass filtering and damping vibration isolation.When the grain feeding rate was 2 kg/s,the natural vibration amplitude of the sensor after difference was about 0.02 V and evenly distributed around the zero voltage 0.2 V.The influence of positive and negative offset on the average value of grain impact signal could be ignored,and the signal-to-noise ratio was increased from 29.21 dB to 62.49 dB.The results of field experiments showed that the yield map drawn can clearly display the yield value of the harvest area,which is used to guide agricultural production.

具有智能电致变色功能的镍钴双金属氢氧化物电极基柔性镍锌电池用于可视化监测剩余电量

具有电化学变色功能的柔性电池在智能电子领域显示出巨大的应用潜力.然而,具有可视化电量预警功能的镍锌电池目前尚未见报道.在此,我们设计了一种用于柔性镍锌电池的电致变色镍钴氢氧化物/镍/氧化铟锡(NiCo BH/Ni/ITO)柔性电极.通过优化Ni层厚度,电极在电流密度为0.1 mA cm^(-2)时,着色效率为59.89 cm^(2)C^(-1),容量为7.15μA h cm^(-2).相应组装的电致变色镍锌电池功率密度为160μW cm^(-2)时,能量密度为12.69μW h cm^(-2),优于部分文献报道的透明柔性超级电容器和电致变色电池.值得注意的是,组装的镍锌电池在充放电过程中显示出可逆的颜色变化,提供了一种可视化监测电池剩余电量的新功能.

Role of the bone marrow vascular niche in chemotherapy for MLL-AF9-induced acute myeloid leukemia

Leukemia stem cells in acute myeloid leukemia(AML)can persist within unique bone marrow niches similar to those of healthy hematopoietic stem cells and resist chemotherapy.In the context of AML,endothelial cells(ECs)are crucial components of these niches that appear to promote malignant expansion despite treatment.To better understand these interactions,we developed a real-time cell cycle-tracking mouse model of AML(Fucci-MA9)with an aim of unraveling why quiescent leukemia cells are more resistant to chemotherapy than cycling cells and proliferate during disease relapse.We found that quiescent leukemia cells were more prone to escape chemotherapy than cycling cells,leading to relapse and proliferation.Importantly,post-chemotherapy resting leukemia cells tended to localize closer to blood vessels.Mechanistically,after chemotherapy,resting leukemia cells interacted with ECs,promoting their adhesion and anti-apoptotic capacity.Further,expression analysis of ECs and leukemia cells during AML,after chemotherapy,and after relapse revealed the potential of suppressing the post-chemotherapy inflammatory response to regulate the functions of leukemia cells and ECs.These findings highlight the role of leukemia cells in evading chemotherapy by seeking refuge near blood vessels and provide important insights and directions for future AML research and treatment.

单组元推力器固定床催化分解反应工程基础

自20世纪60年代肼类化学单组元推力器诞生以来,液体单组元推进技术在卫星轨控、火箭姿态调整和应急动力系统中得到了广泛应用。化学单组元推进技术关键是高能液体化学推进剂在颗粒固定床内催化分解反应过程。由于其化学反应过程的复杂性,目前该类推进技术开发不考虑化学反应工程本质,以热能和空气动力学工程理论为基础,通过大量耗时耗力推力器热实验完成。本工作从化学反应工程角度出发,论述了化工热力学、催化反应动力学、单颗粒催化剂内扩散?反应、催化剂纳微孔道内流体?反应以及在固定床宏观多孔介质中和颗粒堆积形成的介观复杂几何结构内流动?传递?反应的耦合理论,且在化学单组元推进系统中推进剂能量设计,催化剂结构和催化分解固定床设计中的应用。本工作给出了单组元推进技术中相关催化反应工程理论基础,有望为新型绿色化学单组元推进技术的开发提供推进剂配方,为催化剂合成以及分解固定床的设计提供理论基础。

Institutional Investors, Earnings Quality and Asset Liquidity： Evidence from China＇s Stock Market

This paper investigates how institutional holding and earnings quality influence the liquidity of assets. Contrary to findings in developed markets, we document several novel results in China＇s stock market： （1） institutional holding negatively affects assets＇ liquidity, （2） earnings quality is negatively related with liquidity. Since earnings quality captures asymmetric information, low earnings quality induces high divergence in investor opinions and thus boosts market trading, and （3） interestingly, the effect of earnings quality on liquidity is greater if institutional investors＇ holding is at a high level. Overall, our findings cast doubt on the conventional wisdom that institutional investors and earnings quality improve market liquidity. The results are robust to different measures and alternative model specifications.

A Case of Inflammatory Fibroid Polyp with an Elongated Shape in Cecum

Inflammatory fibroid polyp （IFP） is a group of rare benign mesenchymal tumors throughout the gastrointestinal tract.The most involved sites are stomach and large intestines,followed by small intestines,esophagus,and anal canal.However,even in the stomach,its incidence is only 0.1% of all gastric polyps.[1] We here reported an IFP located in the cecum.

A novel Sn-based coordination polymer with high-efficiency and ultrafast lithium storage

Recently,Coordination Polymers(CPs)have been widely utilized as energy storage materials for reversible Lithium-Ion Batteries(LIBs)benefiting from their tunable building blocks and adjusted electrochemical properties.However,the unsatisfied electrochemical behavior of CPs with poor conductivity and sluggish ion transport kinetics is still a bottle-neck for their large-scale energy storage applications in LIBs.Herein,we display the rational fabrication of a conductive Sn-based coordination polymer(Sn-DHTPA)via judiciously choosing suitable building units.The Sn-DHTPA is employed as anode for LIBs,exhibiting superior reversible storage capacity of 1142.6 m A h g^(-1) at 0.1 A g^(-1) after 100 cycles and impressive rate storage capability of 287.7 m A h g^(-1)at 20 A g^(-1).More importantly,a robust cycling performance of 205.5 m A h g^(-1) at an extra-high current density of 20 A g^(-1) are observed without remarkable capacity-fading up to1000 cycles.The behavior superiority of Sn-DHTPA is related to its advanced architecture with abundant lithium storage sites,high electrical conductivity and rapid lithium transport.A series of ex-situ characterizations reveal that the impressive lithium storage capacity is contributed by the redox active sites of both the aromatic linker and metal center related to in-situ generated metallic nanoparticles dispersed in the skeleton.

A benign lesion similar to breast cancer

To the Editor:We here reported a case of a breast lesion found by rapid pathological examination of frozen sections on February 2, 2018.The lesion was very similar to breast cancer in terms of gross observation and histological features.Immunohistochemistry and phos-phatidylinositol-3-kinase (PIK3CA) gene sequencing were performed.The clinicopathological features of the lesion were reported in detail.

Somatic mutation landscape of a meningioma and its pulmonary metastasis

Background:Extracranial metastasis(ENM)of meningiomas is extremely rare,and typically occurs several years after a primary tumor is diagnosed.However,the genetic changes underlying ENM events have not yet been investigated.Case presentation:A 58-year-old male patient was sent to the emergency room of our hospital because of a sudden fall.Magnetic resonance imaging detected a mass at the right frontal sagittal sinus.He underwent tumor resection and recovered well,but post-operative computed tomography revealed three lumps on the right side of his chest.Thoracic surgery was performed to remove two of the lumps.Pathological findings revealed that the brain and lung tumors were grade I meningiomas.The patient received no additional radiation or chemotherapy post-surgery,and there was no sign of tumor recurrence in the brain or progression of the remaining lump in the chest 1 year after surgery.We performed whole exome sequencing of the patient’s blood,primary brain tumor,and lung metastatic tumor tissues to identify somatic genetic alterations that had occurred during ENM.This revealed that a frameshift deletion of the neurofibromin 2 gene likely drove formation of the meningioma.Surprisingly,we found that the brain tumor was relatively homogeneous and contained only one dominant clone;both the pulmonary metastasis and the original brain tumor were derived from the same clone,and no obvious additional driver mutations were detected in the metastatic tumor.Conclusion:Although ENM of meningiomas is very rare,brain tumor cells appear to be more adaptable to tissue microenvironments outside of the central nervous system than was commonly thought.

China＇s Nonfinancial Corporate Debt Dynamics

Since the global financial crisis broke out in 2008, China＇s nonfinancial corporate debt has been rising steadily and rapidly, posing serious threat to China ＂s financial stability. China ＂s rising corporate debt is mainly attributable to three factors： worsening capital efficiency, worsening corporate profitability and high funding costs. Based on a dynamic recursive model developed in the paper, we simulate the trajectories of China＇s corporate debt-to- GDP ratio, and find that if China fails to reverse the current trends in capital efficiency, corporate profitability and financing costs, China ＂s nonfinancial corporate debt-to-GDP ratio will continue to rise without converging to a limit. Against most economists ＇ intuition, given the current trends of changes in parameters, higher economic growth will not help China to escape the corporate debt trap. On the contrary, it will make China ＂s corporate debt problem even worse. To avert a corporate debt crisis, China needs to speed up the structural reform and change the growth paradigm so as to enhance capital efficiency and firms＇ profitability, while reducing firms ＇financing costs.

2008表坛趋势回顾

全球性的不景气,连奢华产业如高级制表亦受到不少冲击。但2008的表坛无疑是精彩的,陀飞轮的数量少了点,但各种概念与技术性的突破却未减反增。2008也许对钟表品牌是个相对低迷的一年,但对买家与表迷而言,可能反而是很精彩的一年。这里我们尝试分析2008年的表坛,找出一些值得关注的趋势。